Vitamin D3 is synthesized in the skin from 7-dihydrocholesterol and then hydroxylated to 25-hydroxyvitamin D3 in the liver and, subsequently in the kidney, to the most active hormonal form of vitamin D3, namely, 1?,25-dihydroxy vitamin D3 (1?,25-(OH)2D3, calcitriol). It has been established that 1?,25-(OH)2D3 stimulates intestinal calcium absorption and mobilizes calcium from bone. Recently, an important function of 1?,25-(OH)2D3 in monocytic differentiation of human promyelocytic leukemia cells (HL-60) has been discovered. Recently, 20-hydroxy and alkoxy analogs of 1?,25-(OH)2D3 have been described and are being examined as potential drugs for osteoporosis (e.g. ED-71). We prepared both 2?- and 2?-hydroxy analogs of 19-nor-1?,25-(OH)2D3 and their alkoxy derivatives. These analogs exhibited selective calcemic activity and, moreover, showed high HL-60 differentiation activity. In our continuing investigation of structure-activity relationship of the vitamin D molecule, we have also synthesized 1?- and 2??-alkyl and hydroxyalkyl analogs of 19-nor-1?,25-(OH)2D3. Configurations of the A-ring fragment substituents were determined by 1H, 1H COSY 2D spectra and 1H NOE difference NMR spectroscopy.